The AD7c-NTP neuronal thread protein biomarker for detecting Alzheimer's disease
The AD7c-NTP neuronal thread protein biomarker for detecting Alzheimer's disease
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DOI：
10.3233/jad-2001-3310
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发表时间：
2001-01-01
影响因子：
4
通讯作者：
Wands, Jack R.
中科院分区：
文献类型：
--
作者：
de la Monte, Suzanne M.;Wands, Jack R.
阿尔茨海默病（AD）中的痴呆最终是由于由几种机制介导的细胞损失，包括细胞凋亡、线粒体功能受损和可能的坏死。痴呆的第二个主要神经解剖学相关性是异常皮质神经炎发芽，伴有营养不良神经突的大量增殖。AD的早期体内检测将需要高度敏感和相对特异的生物标志物的非侵入性测定，这些生物标志物反映了细胞功能的这些基本异常。AD相关的神经元丝蛋白（AD 7 c-NTP）基因编码一个类似于41 kD的跨膜磷蛋白，导致转染的神经元细胞凋亡和神经炎发芽。AD 7 c-NTP基因在AD中在病程早期开始过表达。在大脑中，增加的AD 7 c-NTP免疫反应性与磷酸化tau免疫反应性细胞骨架病变相关，但与淀粉样蛋白β积累无关。死后脑组织中的AD 7 c-NTP水平与配对脑室液样品中测量的水平相关，表明该蛋白质由垂死细胞分泌或释放到脑脊液（CSF）中。在这方面，在早期或中度重度AD患者的CSF和尿液中均可检测到升高的AD 7 c-NTP水平，并且CSF和尿液中AD 7 c-NTP水平与痴呆的严重程度相关。AD 7 c-NTP检测的最新配置，称为“7 c Gold”，对于检测早期AD具有大于90%的灵敏度和特异性。许多研究的综合结果表明，AD 7 c-NTP是一种极好的生物标志物，可能有助于对有AD风险的老年患者进行常规临床评估。
Dementia in Alzheimer's disease (AD) is ultimately due to cell loss mediated by several mechanisms including, apoptosis, impaired mitochondrial function, and possibly necrosis. A second major neuroanatomic correlate of dementia is aberrant cortical neuritic sprouting with abundant proliferation of dystrophic neurites. Early in vivo detection of AD will require non-invasive assays of highly sensitive and relatively specific biomarkers that reflect these fundamental abnormalities in cellular function. The AD-associated neuronal thread protein (AD7c-NTP) gene encodes a similar to 41 kD membrane-spanning phosphoprotein that causes apoptosis and neuritic sprouting in transfected neuronal cells. The AD7c-NTP gene is over-expressed in AD beginning early in the course of disease. In the brain, increased AD7c-NTP immunoreactivity is associated with phospho-tau-immunoreactive cytoskeletal lesions, but not with amyloid-beta accumulations. The levels of AD7c-NTP in postmortem brain tissue correlate with the levels measured in paired ventricular fluid samples, suggesting that the protein is secreted or released by dying cells into cerebrospinal fluid (CSF). In this regard, elevated levels of AD7c-NTP can be detected in both CSF and urine of patients with early or moderately severe AD, and the CSF and urinary levels of AD7c-NTP correlate with the severity of dementia. The newest configuration of the AD7c-NTP assay, termed "7c Gold", has greater than 90% sensitivity and specificity for detecting early AD. The aggregate results from a number of studies suggest that AD7c-NTP is an excellent biomarker that could be helpful in the routine clinical evaluation of elderly patients at risk for AD.